Fertility management in mammals is a global issue of agricultural, economic and social importance. Conventional approaches of preventing pregnancy are surgical, can cause morbidity and mortality, and are unacceptable in some countries. Other approaches to contraception include the use of various hormones to regulate the ovulatory cycle and which may be associated with certain side effects. Still other approaches to contraception include the use of zona pellucida proteins as immunocontraceptives to induce permanent or transient infertility.
The decapeptide luteinizing hormone releasing hormone (LHRH) is the key regulatory brain peptide that controls reproduction in mammals and, thus, is a logical target for devising approaches to contraception. The endocrine effects of active immunization against LHRH have been studied in a variety of young and adult male and female animals (Adams et al., Biol. Reprod. 35:360, (1986); Esbenshade et al., Biol. Reprod. 33:569, (1985); Garza et al., Biol. Reprod. 35:347, (1986); Johnson et al., J. Anim. Sci. 66:719, (1988); Schanbacher et al., Am. J. Physiol. 242:3201, (1985)). These studies demonstrated decreases in gonadotropins, sperm production, follicular development, ovulation and conception after immunization against LHRH chemically conjugated to a carrier protein.
Johnson et al., J. Anim. Sci. 66:719, (1988) developed a conjugated ovalbumin LHRH molecule which, when used with Complete Freund's Adjuvant (CFA), was 100% effective in preventing pregnancy in a limited number of animals. However, in a commercial application in Australia, LHRH conjugated to ovalbumin (Vaxtrate.RTM.) prevents only 80% of pregnancies of heifers (Hoskinson et al., Austral. J. Biotech. 4:166-176 (1990)).
Although immunoneutralization of LHRH by a chemically conjugated vaccine could provide a safe, humane and effective approach to preventing reproduction, such vaccines face considerable obstacles to approval for use in the United States. Such obstacles arise from the fact that chemical conjugation does not produce an antigen with a homogenous known structure within and between batches. Therefore, there remains a need for a vaccine directed to reproduction related polypeptides such as the hypothalamic hormone LHRH and the pituitary gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH), which vaccines have known reproducible structures.